This project investigates the neural mechanisms underlying individual differences in how amphetamine affects mood and behavior. Preliminary data from our group and others indicates that euphoric mood and risk-related behaviors, common following amphetamine intake, vary in their occurrence and magnitude among people. Response to amphetamines, which tends to be stable over time, appears to be modulated by personality and gender. Recent placebo controlled studies indicate that the personality trait of fearless sensation seeking is a very strong predictor of the magnitude of amphetamine's effect on physiological outcomes and euphoric mood. Between-person differences in the behavioral effects of amphetamine are less well understood, but amphetamine effects appear to be stronger in males and also among extroverted people, who are particularly sensitive to environmental reward. The objective of the current application is to investigate the neural foundations of these individual differences and gender effects, using a pharmacological challenge design and fMRI neuroimaging methods. The study utilizes a two-session, placebo-controlled amphetamine administration procedure. fMRI scans are timed during the peak period of drug effects. Individual differences in amphetamine-induced BOLD signal are assessed on two tasks: the Balloon Analogue Risk Task (BART) and International Affective Picture Set (IAPS), which test behavioral impulsivity and emotional reactivity, respectively. Sixty participants (half female) will be assessed, and participants will vary along a normal distribution of scores on Tellegen's Agentic Positive Emotionality and Harm Avoidance, the two robust, empirically derived measures of extraversion and fearless sensation seeking that predict up to 40% - 50% of the variation in the acute impulsive and euphoric effects of amphetamine in previous samples. The major aims of the study are to investigate individual differences in amphetamine-induced increase in the neural activity and regions of activation associated with reward-related and punishment-related signal processing relevant to the drug's effects on mood and behavior. The study has public health significance as it identifies neural predictors underlying the biobehavioral vulnerability to psychostimulants in otherwise healthy individuals. This goal is important given the increasingly problematic use of amphetamines by adolescents and young adults nation-wide. [unreadable] [unreadable] [unreadable]